Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis

Xiang Liu, Dahn L. Clemens, James A. Grunkemeyer, Jeffrey D. Price, Kelly O’Connell, Nora M. Chapman, Peter Storz, Haitao Wen, Jesse L. Cox, Whitney L. Reid, Michael A. Hollingsworth, Sarah Thayer

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Abstract

The Muc-1 oncoprotein is a tumor-associated mucin often overexpressed in pancreatic cancer. We report that knockout of Muc-1 reduced the degree of pancreatic inflammation that resulted from infection with Coxsackievirus B3 (CVB3) in a mouse model. CVB3-infected Muc-1-deficient (Muc-1KO) mice had significantly reduced infiltration of macrophages into the murine pancreas. We found that Muc-1 signaling through NF-κB increased expression of ICAM-1, a pro-inflammatory mediator that recruits macrophages. Further investigation revealed that bone marrow derived macrophages (BMDM) from the Muc-1KO mice exhibited defective migration properties, in part due to low expression of the C-C motif chemokine receptor (CCR2) and the integrin Very Late Antigen 4 (VLA-4). The results presented here provide novel insight into the role of Muc-1 in regulating the inflammatory response and the cellular microenvironment in pancreatitis.

Original languageEnglish (US)
Article number10656
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

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Cite this

Liu, X., Clemens, D. L., Grunkemeyer, J. A., Price, J. D., O’Connell, K., Chapman, N. M., Storz, P., Wen, H., Cox, J. L., Reid, W. L., Hollingsworth, M. A., & Thayer, S. (2019). Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis. Scientific reports, 9(1), [10656]. https://doi.org/10.1038/s41598-019-46933-y